Knocking down RAD51AP1 enhances chemosensitivity by inhibiting the self-renewal of CD133 positive ovarian cancer stem-like cells.

PURPOSE: This study was designed to investigate the function of RAD51AP1 in the self-renewal and chemosensitivity of CD133 positive (CD133+) ovarian cancer (OC) stem-like cells. METHODS: CD133+ (CD133 positive) OVCAR4 and CD133 negative (CD133-) OVCAR4 cells were separated from OVCAR4 by flow cytometry. Then, the separated CD133+OVCAR4 cells were divided into the following groups: Vector group; RAD51AP1 group; siNC group; si-RAD51AP1 group. Next, sphere-formation assay and colony forming assay were used to evaluate the self-renewal and proliferation ability of cells; western blot to detect the expression of RAD51AP1, transforming growth factor beta 1 (TGF-ß1) and SMAD4 proteins in tissues and cells; qRT-PCR to assess the mRNA levels of sex-determining region Y-box 2 (SOX2), octamer-binding transcription factor 4 (OCT4), NANOG and Kruppel-like factor 4 (KLF4). RESULTS: The performance of CD133+OVCAR4 cells was much better than that of CD133-OVCAR4 cells in sphere-formation assay and colony forming assay. Besides, compared with adjacent group and CD133-OVCAR4 cells, the expression level of RAD51AP1 increased significantly in OC group and CD133+OVCAR4 cells. Moreover, the over-expression of RAD51AP1 promoted the self-renewal and proliferation of CD133+OVCAR4 cells. On the contrary, knocking down the expression level of RAD51AP1 could inhibit the self-renewal and proliferation of CD133+OVCAR4 cells and improve the sensitivity of cells to chemotherapy drugs. CONCLUSION: The findings of this study showed that RAD51AP1 was highly expressed in OC tissue and CD133+OVCAR4 cells, and regulated the self-renewal and chemosensitivity of tumor cells through the TGF-ß1/SMAD4 signaling pathway.

Ruxolitinib reduces severe CRS response by suspending CAR-T cell function instead of damaging CAR-T cells.

The therapeutic effect of CAR-T is often accompanied by sCRS, which is the main obstacle to the promotion of CAR-T therapy. The JAK1/2 inhibitor ruxolitinib has recently been confirmed as clinically effective in maintaining control over sCRS, however, its mechanism remains unclear. In this study, we firstly revealed that ruxolitinib significantly inhibited the proliferation of CAR-T cells without damaging viability, and induced an efficacy-favored differentiation phenotype. Second, ruxolitinib reduced the level of cytokine release not only from CAR-T cells, but also from other cells in the immune system. Third, the cytolytic activity of CAR-T cells was restored once the ruxolitinib was removed; however, the cytokines released from the CAR-T cells maintained an inhibited state to some degree. Finally, ruxolitinib significantly reduced the proliferation rate of CAR-T cells in vivo without affecting the therapeutic efficacy after withdrawal at the appropriate dose. We demonstrated pre-clinically that ruxolitinib interferes with both CAR-T cells and the other immune cells that play an important role in triggering sCRS reactions. This work provides useful and important scientific data for clinicians on the question of whether ruxolitinib has an effect on CAR-T cell function loss causing CAR-T treatment failure when applied in the treatment of sCRS, the answer to which is of great clinical significance.

SNHG16 lncRNAs are overexpressed and may be oncogenic in human gastric cancer by regulating cell cycle progression.

The small nucleolar RNA host gene 16 (SNHG16) has recently been shown to be a putative oncogene in gastric cancer (GC) and other cancer types, but how its four lncRNA variants are expressed in any physiological and pathological situation remains unknown. To investigate the expression and function of the four lncRNA variants of SNHG16, mainly the variant 1, in GC, we performed quantitative PCR to determine the RNA levels of the four variants in 60 GC tissue samples and several cell lines. We also studied how knocking down of SNHG16 with siRNA affected proliferation, apoptosis, cell cycle progression, as well as migration and invasion of GC cells. Our results showed that variants 1 and 4 were overexpressed in GC tissues compared with adjacent uninvolved tissues. Knockdown of the four variants, mainly the variant 1, enhanced apoptosis and inhibited cell cycle progression of a GC cell line by arresting the cells at the G1 phase. These cellular effects were associated not only with decreased protein levels of c-Myc, PCNA, cyclins D1, E1, A2 and B, as well as CDKs 2 and 6, but also with increased protein levels of the p21, p27 and p53. Knockdown of total SNHG16 lncRNAs also inhibited invasion and migration of the GC cells in vitro. These results collectively suggest that SNHG16 may be oncogenic in GC by regulating cell cycle progression and may serve as a GC biomarker.

[Alternative Splicing Analysis of LACTB Gene and Expression Characteristics of Different Transcripts in Leukemia Cell Lines].

OBJECTIVE: To detect the expression of different transcripts of lactamase ß（LACTB) gene in leukemic cell lines. METHODS: NCBI website and DNAstar software were used to detect the Bioinformatics analysis of LACTB. The expression of different transcripts of LACTB gene in leukemic cell lines (THP-1, HL60, K562, U937, Jurkat and Raji) was detected by reverse transcription PCR (RT-PCR), DNA and clone sequencing; the expression of different transcripts of LACTB gene in leukemic cell lines was detected by Quantitative Real-time PCR. RESULTS: There were a variety of splicing isomers in LACTB, and it could produce a variety of protein isomers with conserved N-terminal and different C-terminal, moreover, there were many splice isoforms of LACTB in leukemia cell lines, and there were different expression patterns in different cell lines, including XR1, V1, V2 and V3. The expression of total LACTB showed high in HL60 cells, while low in Raji cells, and the difference was statistically significant (P<0.05). The V1 was high expression in U937 cells but low in Raji cells, and the difference was statistically significant (P<0.05). V2 was high expression in HL60 cells but lowly in Raji cells, and the difference was statistically significant (P<0.05). The expression of V3 was low in THP-1 cells, which was significantly different as compared with that in normal bone marrow (P<0.05). CONCLUSION: The reaserch found that there are many splice isomers of LACTB in leukemic cell lines, and there are different expression patterns in different cell lines.

[Staged surgery of Sanders type â £ calcaneal fractures with soft tissue three-degree swelling].

OBJECTIVE: To compare the clinical efficacy of staged surgery on Sanders Ⅳ calcaneal fractures with soft tissue Ⅲ swelling. METHODS: The clinical data of 76 patients with Sanders type Ⅳ closed calcaneal fracture with soft tissue three-degree swelling treated from June 2017 to May 2020 was retrospectively analyzed, including 54 males and 22 females, aged from 25 to 50 (38.16±10.24) years. The patients were divided into observation group and control group according to different treatment methods. Twenty-four patients in the observation group were treated by staged surgery stageⅠclosed prying traction reduction and Kirschner wire fixation, stageⅡopen reduction and internal fixation with titanium plate, including 17 males and 7 females, aged from 25 to 50 (36.12±9.56) years. There were 52 patients in the control group, including 37 males and 15 females, aged from 25 to 50 (38.32±10.67) years, these patients were treated with open reduction and internal fixation with titanium plate after the dermatoglyphic signs appeared. The swelling subsidence time, the length of hospitalization days, and the incidence of postoperative incision complications were compared between two groups. The Bhler angle, Gissane angle, and calcaneal varus angle were measured by X-ray before and 6 months after operation. American Orthopedic Foot and Ankle Society (AOFAS) about the ankle hindfoot score was used to evaluate the clinical efficacy. RESULTS: All 76 patients were followed up for 8 to 12 (9.52±2.01) months. The swelling subsidence time and hospitalization days in observation group were (12.12± 3.24) d and (24.53±6.44) d, respectively, which in control group were (15.16±4.16) d and (29.46±9.61) d, with statistical difference between two groups (P<0.05). Postoperative 6 months, Bhler angle, Gissane angle and calcaneal varus angle were (31.33±10.15)°, (145.34±8.04) ° and (10.31±3.23) ° in observation group, while those in control group were (20.24±8.23) °, (165.28±10.29) °and (21.24±5.27) °, with statistical difference between two groups (P<0.05). And there was significant difference in all patients between before and 6 months after operation (P<0.05). The AOFAS score of the observation group and control group were 71.76±9.84 and 57.23±10.76 at 6 months after operation, with significant different between two groups (P< 0.05). The excellent rate of observation group was significantly higher than that of control group (P<0.05). CONCLUSION: Compared with open reduction and internal fixation with titanium plate after the appearance of dermatoglyphic signs, staged surgery for Sanders type Ⅳ calcaneal fractures with soft tissue three-swelling does not increase the risk of soft tissue complications, and can significantly shorten the patient's swelling subsidence time and hospitalization days, improve the quality of fracture reduction and short term function, and relieve pain.

Phytotoxic mechanism of allelochemical liquiritin on root growth of lettuce seedlings.

As the main active ingredient of the traditional Chinese medicine Glycyrrhiza uralensis Fisch, liquiritin has multiple biological activities, including anti-inflammatory, antihepatotoxicity, immune regulation, anti-virus and anti-cancer. In addition, liquiritin has been recognized as an allelochemical that displays markedly inhibitory effects on the growth of target plants, G. uralensis and lettuce. However, its phytotoxic mechanism remains unknown. In the present study, the mode of action of liquiritin against root growth of lettuce seedling was researched. After treatments with liquiritin, the cell division in root tips of lettuce seedlings was partly arrested, and the cell viability and root vitality were obviously lost. At the same time, overproduction of reactive oxygen species (ROS), malondialdehyde (MDA) and proline (Pro) in lettuce seedlings were induced by liquiritin. The results indicated that the phytotoxic effects of liquiritin was probably dependent on the induction of ROS overproduction, resulting in membrane lipids peroxidation following with cell death and mitosis process disorder.

Effect of exogenous gonadotropin on the transcriptome of human granulosa cells and follicular fluid hormone profiles.

BACKGROUND: Superovulation treatment had some adverse effects on maturity and development of oocytes. Can superovulation dose of gonadotropins (Gns) affect the transcriptome of granulosa cells and follicular fluid (FF) hormone levels? METHODS: One leading pre-ovulatory follicle per subject was used from three natural-cycle and four Gn-stimulated patients. Granulosa cells and FF samples were collected from the same leading follicle of each patient. RNA was extracted from granulosa cells and subjected to deep sequencing and analysis. Follicle-stimulating hormone (FSH), estradiol (E2), androstenedione (AND), testosterone (T), luteinizing hormone (LH), and progesterone (P4) levels in FF were measured by immunoassays. Student's t test was used for statistical analysis. RESULTS: A total of 715 genes were up-regulated, and 287 genes were down-regulated, in the Gn-stimulated group relative to the control group. Gene Ontology analysis revealed that the down-regulated genes were enriched in cell cycle and meiosis pathways, primarily those associated with follicle or oocyte maturation and quality. On the other hand, the up-regulated genes were enriched in functions related to immunity and cytokine-cytokine receptor interactions. Compared to the follicles of natural cycle, the E2 and LH concentrations were significantly reduced (P < 0.001), the P4 concentration was significantly increased (P = 0.003), and the concentrations of FSH, T and AND had no difference in the follicles of Gn-stimulated cycle. CONCLUSIONS: Cell cycle- and meiosis-associated genes were down-regulated by Gns stimulation, whereas immune- and cytokine-associated genes were up-regulated. Hormone levels were also affected by Gns stimulation. Compared with natural-cycle follicles,putative markers associated with oocyte quality and follicle maturation were significantly different from those in Gn-stimulated follicles. Hormone levels in follicles were compatible with the steroidogenic patterns of granulosa cell, which reflects the follicle maturation and oocyte quality.

SIRT1 and FOXO Mediate Contractile Differentiation of Vascular Smooth Muscle Cells under Cyclic Stretch.

BACKGROUND/AIMS: Physiological mechanical stretch in vivo helps to maintain the quiescent contractile differentiation of vascular smooth muscle cells (VSMCs), but the underlying mechanisms are still unclear. Here, we investigated the effects of SIRT1 in VSMC differentiation in response to mechanical cyclic stretch. METHODS AND RESULTS: Rat VSMCs were subjected to 10%-1.25Hz-cyclic stretch in vitro using a FX-4000T system. The data indicated that the expression of contractile markers, including α-actin, calponin and SM22α, was significantly enhanced in VSMCs that were subjected to cyclic stretch compared to the static controls. The expression of SIRT1 and FOXO3a was increased by the stretch, but the expression of FOXO4 was decreased. Decreasing SIRT1 by siRNA transfection attenuated the stretch-induced expression of contractile VSMC markers and FOXO3a. Furthermore, increasing SIRT1 by either treatment with activator resveratrol or transfection with a plasmid to induce overexpression increased the expression of FOXO3a and contractile markers, and decreased the expression of FOXO4 in VSMCs. Similar trends were observed in VSMCs of SIRT1 (+/-) knockout mice. The overexpression of FOXO3a promoted the expression of contractile markers in VSMCs, while the overexpression of FOXO4 demonstrated the opposite effect. CONCLUSION: Our results indicated that physiological cyclic stretch promotes the contractile differentiation of VSMCs via the SIRT1/FOXO pathways and thus contributes to maintaining vascular homeostasis.

Salidroside prevents cognitive impairment induced by chronic cerebral hypoperfusion in rats.

OBJECTIVE: To investigate the effects of salidroside on cognitive dysfunction induced by chronic cerebral hypoperfusion in rats. METHODS: Male Sprague-Dawley rats (n = 36) were divided into three groups (n = 12 per group): sham operation; bilateral permanent occlusion of the common carotid arteries (2-VO); 2-VO + salidroside. Rats received 20 mg/kg per day salidroside or vehicle intraperitoneal injection beginning the day before surgery and continuing until 34 days postoperatively. Cognitive function was evaluated by Morris water maze test and hippocampal long-term potentiation (LTP) measurement. Hippocampal neuronal apoptosis was evaluated via immunofluorescence. RESULTS: Chronic cerebral hypoperfusion caused marked cognitive deficit and LTP inhibition. These effects were largely ameliorated by salidroside administration. Salidroside prevented caspase-3 activation, increased the ratio of Bax/Bcl-2, and reversed hippocampal neuronal loss induced by chronic cerebral hypoperfusion. CONCLUSIONS: Salidroside prevents cognitive deficits caused by chronic cerebral hypoperfusion in rats, and alleviates apoptosis in the hippocampal CA1 area.

The role of SIRT6 in the differentiation of vascular smooth muscle cells in response to cyclic strain.

Vascular smooth muscle cells (VSMCs) may switch their phenotype between a quiescent contractile phenotype and a synthetic phenotype in response to cyclic strain, and this switch may contribute to hypertension, atherosclerosis, and restenosis. SIRT 6 is a member of the sirtuin family, and plays an important role in different cell processes, including differentiation. We hypothesized that cyclic strain modulates the differentiation of VSMCs via a transforming growth factor-ß1 (TGF-ß1)-Smad-SIRT6 pathway. VSMCs were subjected to cyclic strain using a Flexercell strain unit. It was demonstrated that the strain stimulated the secretion of TGF-ß1 into the supernatant of VSMCs. After exposed to the strain, the expressions of contractile phenotype markers, including smooth muscle protein 22 alpha, alpha-actin, and calponin, and phosphorylated Smad2, phosphorylated Smad5, SIRT6 and c-fos were up-regulated in VSMCs by western blot and immunofluorescence. And the expression of intercellular-adhesion molecule-1 (ICAM-1) was also increased detected by flow cytometry. The strained-induced up-regulation of SIRT6 was blocked by a TGF-ß1 neutralizing antibody. Furthermore, the effects of strain on VSMCs were abrogated by SIRT6-specific siRNA transfection via the suppression c-fos and ICAM-1. These results suggest that SIRT6 may play a critical role in the regulation of VSMC differentiation in response to the cyclic strain.

Endothelial insulin-like growth factor-1 modulates proliferation and phenotype of smooth muscle cells induced by low shear stress.

Endothelial cells (ECs) are directly exposed to shear stress and modulate the neighboring vascular smooth muscle cells (VSMCs), which plays important roles in vascular remodeling during atherosclerosis. Our previous research revealed that insulin-like growth factors (IGFs) might participate in low shear stress (LowSS) induced vascular remodeling, which remains to be elucidated. Using EC/VSMC co-cultured parallel-plate flow chamber, LowSS (5 dyn/cm(2)) was applied and normal shear stress (NSS, 15 dyn/cm(2)) was used as control. LowSS induced IGF-1 secretion from ECs, which subsequently phosphorylated IGF-1 receptor (IGF-1R) on co-cultured VSMCs, then increased Akt phosphorylation and Sirt2 expression. Decreasing IGF-1 in ECs by RNA interference (RNAi) reversed these effects on VSMCs. Exogenous IGF-1 increased IGF-1R and Akt phosphorylation, Sirt2 expression, and proliferation of VSMCs, and induced VSMCs towards synthetic phenotype. PI3 K/Akt specific inhibitor wortmannin decreased Sirt2 expression, proliferation, and synthetic phenotype transformation of VSMCs, but had no effect on IGF-1R. Sirt2 RNAi repressed VSMC proliferation and phenotypic transformation, but had no effect on IGF-1R and Akt. Taken together, LowSS induces the secretion of IGF-1 from ECs, which subsequently paracrine influences the co-cultured VSMCs via IGF-1R and Akt phosphorylation, and Sirt2 expression, then results in the proliferation and synthetic phenotype transformation.

SIRT1 is highly expressed in brain metastasis tissues of non-small cell lung cancer (NSCLC) and in positive regulation of NSCLC cell migration.

Brain metastases are a frequent and ongoing major complication of non-small cell lung cancer (NSCLC). To deepen our understanding to the underlying mechanisms by which NSCLC cells metastasize to brain and hence to improve the therapy, a high throughput RNAi screening with shRNA library of 153 epigenetic genes was subjected to A549, a NSCLC cell line with high migration ability, to examine the effects of these genes on cell migration by wound-healing assay. The screening results showed that knockdown of 2 genes (KDM5B and SIRT1) dramatically and specifically inhibits A549 migration but not affects the proliferation, which was subsequently confirmed through transwell migration assay. Furthermore, SIRT1 is found to be highly expressed in brain metastasis tissues of NSCLC, compared to the NSCLC tissues, suggesting that SIRT1 may play roles in brain metastasis of NSCLC. The relationship between SIRT1 expression and cell migration ability was further investigated in three NSCLC cell lines and the result indicated that SIRT1 expression is tightly correlated with cell migration ability. Collectively, our work provides potential biomarker and therapeutic target for brain metastasis of NSCLC.

[Real-time CT of upper airway in patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To explore the technology and clinical application of real-time CT scan in obstructive sleep apnea hypopnea syndrome during awake and drug induced sleep state. METHODS: Sixty-two patients with OSAHS diagnosed by polysomnography underwent 256 layer spiral CT scan during awake and drug-induced sleep apnea state, and multiplanar reconstruction and volume rendering of computed tomography images were performed. To observe the dynamic changes of upper airway and locate the sites of airway obstruction in patients with OSAHS, the minimum section area, diameter and volume of pharynx cavity were measured on reconstructed 3-dimensional computed tomography. RESULTS: Real-time CT scans were completed successfully in all of the patients. It was revealed that airway obstruction frequently occurred at retropalatal and retroglottal region. Real-time CT scans revealed 29 cases with airway obstruction at isolated retropalatal region, 19 cases with airway obstruction at retropalatal and retroglottal region simultaneously, 6 cases with airway obstruction at retropalatal and epiglottal region simultaneously, 7 cases with airway obstruction at retropalatal, retroglottal and retroglottal region simultaneously, 1 case without airway obstruction. There was no airway obstruction at retroglottal or retroglottal region isolatedly. Rate of single region airway obstruction was 46.8% (29/62), and rate of multiple regions airway obstruction 51.6% (32/62). The real-time CT results showed that starting from Friedman tongue position I to IV, the percentage of obstruction at retroglottal and (or) retroglottal region simultaneously were increasing, the percentage of obstruction were 0/6, 8/25, 13/20, 11/11, respectively (χ(2) = 22.00, P < 0.005). The minimum section area, volume, minimum anteroposterior diameter and left-right diameter of pharynx cavity between awake and drug-induced sleep apnea state had statistically significant difference in all region. CONCLUSIONS: Real-time CT scans in drug-induced sleep state could get more information about the anatomical and pathological changes of upper airway, providing relatively objective morphological basis for the diagnosis and treatment of patients with OSAHS. Therefore, real-time CT scans have important value in practical application.

A novel 7-O-modified genistein derivative with acetylcholinesterase inhibitory effect, estrogenic activity and neuroprotective effect.

To find the multi-target-directed compounds for the treatment of Alzheimer's disease (AD), we synthesized 7-(4-(diethylamino)butoxy)-5-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one, a novel 7-O-modified genistein derivative (GS-14), and investigated its acetylcholinesterase (AChE) inhibitory effect, estrogenic activity and neuroprotective effect. GS-14 acted as a selective AChE inhibitor in vitro, with an IC50 value of 0.17 µM and showed no inhibition activity against butyrylcholinesterase (BuChE). The Lineweaver-Burk plot revealed that GS-14 was a non-competitive AChE inhibitor with a K(i) value of 0.23 µM and the molecular docking model indicated that GS-14 interacted with the peripheral anionic site (PAS) of AChE. The MCF-7 proliferation assay demonstrated that GS-14 possessed estrogenic activity and GS-14 exhibited a high specificity for estrogen receptor ß (ERß) with a dissociation constant (K(i)) of 2.86 nM compared with that of 1.01 µM for estrogen receptor α (ERα) in the molecular docking study. GS-14 also possessed a neuroprotective effect and showed the best protective effect against the ß-amyloid protein-induced injury on SH-SY5Y cells at a concentration of 1 nM. Considering its AChE-inhibition activity, estrogenic activity and neuroprotective effect, GS-14 may be a potential multi-target agent for the treatment of AD.

[Comparison among three reconstruction techniques after distal radical gastrectomy].

OBJECTIVE: To compare surgical efficacy after three different reconstruction techniques after radical resection of distal gastric cancer. METHODS: Clinical data of 169 cases of distal gastric cancer operated in our hospital from 2007 to 2010 were retrospectively analyzed. The reconstruction techniques included Billroth I (anastomosis (n=60), Billroth II (anastomosis (n=41), and Roux-en-Y anastomosis (n=68). Efficacy among 3 groups was compared. Specific symptoms scale was used to evaluate the quality of life in three methods after three months. RESULTS: Compared to Billroth I(anastomosis and Billroth II (anastomosis, Roux-en-Y anastomosis had longer operative time [(266.3±70.4) min vs. (196.2±54.3) min, and (228.5±67.7) min], more blood loss [(220.9±67.6) ml vs. (170.5±61.5) ml and (188.5±76.7) ml], and shorter time to gastric tube removal [(2.6±1.5) d vs. (3.1±1.3) d and (3.6±1.2) d], milder postoperative reflux and heartburn sensation(specific symptoms scale, 1.8±0.4 vs. 1.9±0.6 and 2.6±0.4, P<0.05). CONCLUSIONS: Although Roux-en-Y anastomosis is not consistent with physiological route and the procedure is more complex to perform, it can effectively prevent reflux complications. Roux-en-Y anastomosis is a better reconstruction technique after radical resection of distal gastric cancer.

Drug-eluting microfibrous patches for the local delivery of rolipram in spinal cord repair.

Spinal cord injury (SCI) remains a major challenge for regenerative medicine. Following SCI, axon growth inhibitors and other inflammatory responses prevent functional recovery. Previous studies have demonstrated that rolipram, an anti-inflammatory and cyclic adenosine monophosphate preserving small molecule, improves spinal cord regeneration when delivered systemically. However, more recent studies showed that rolipram has some adverse effects in spinal cord repair. Here, we developed a drug-delivery platform for the local delivery of rolipram into the spinal cord. The potential of drug-eluting microfibrous patches for continuous delivery of high and low-dose rolipram concentrations was characterized in vitro. Following C5 hemisections, athymic rats were treated with patches loaded with low and high doses of rolipram. In general, animals treated with low-dose rolipram experienced greater functional and anatomical recovery relative to all other groups. Outcomes from the high-dose rolipram treatment were similar to those with no treatment. In addition, high-dose treated animals experienced reduced survival rates suggesting that systemic toxicity was reached. With the ability to control the release of drug dosage locally within the spinal cord, drug-eluting microfibrous patches demonstrate the importance of appropriate local release-kinetics of rolipram, proving their usefulness as a therapeutic platform for the study and repair of SCI.

[Comparative study of determining the sites of airway obstruction in obstructive sleep apnea hypopnea syndrome between real-time CT scans and laryngofiberscope technology].

OBJECTIVE: To compare 256-layer spiral computed tomography (CT) scan in sleep and laryngofiberscope technology for locating obstructive sites of upper airway in patients with obstructive sleep apnea hypopnea syndrome, analyze their advantages and disadvantages and discuss the clinical application values. METHODS: A total of 59 patients with OSAHS diagnosed by polysomnography underwent spiral CT scan in awake and drug-induced sleep states and laryngofiberscope examination in awake state to assess the sites of airway obstruction. RESULTS: Real-time CT scans were completed successfully in all patients. There were airway obstruction at isolated retropalatal region (real-time CT revealing n = 26, laryngofiberscope revealing n = 34), retropalatal and retroglottal regions simultaneously (real-time CT revealing n = 19, laryngofiberscope revealing n = 10), retropalatal and epiglottal regions simultaneously (real-time CT revealing n = 6, laryngofiberscope revealing n = 2), retropalatal and retroglottal and epiglottal regions simultaneously (real-time CT revealing n = 7, laryngofiberscope revealing n = 3) and no airway obstruction (real-time CT revealing n = 1, laryngofiberscope revealing n = 10). There was not solitary airway obstruction at retroglottal or epiglottal region. The results of real-time CT scans and laryngofiberscope examination were statistically significant different in all regions, and real-time CT scanning compared with laryngofiberscope found more obstructive sites of upper airway [retropalatal region: 98.3% (n = 58) vs 81.4% (n = 48), χ(2) = 5.82, P < 0.05; retroglottal regions: 44.1% (n = 26) vs 22.0% (n = 13), χ(2) = 9.60, P < 0.01; epiglottal regions: 22.0% (n = 13) vs 8.5% (n = 5), χ(2) = 4.90, P < 0.05]. CONCLUSION: Compared with laryngofiberscope examination,real-time dynamic CT scans in drug-induced sleep state could get more information about anatomy changes of upper airway, providing relatively objective morphological basis for diagnosis and treatment of patients with OSAHS.

[Analysis for myeloperoxidase genetic polymorphism in gastric cancer].

OBJECTIVE: To investigate the association of myeloperoxidase(MPO) genetic polymorphism and gastric cancer. METHODS: A case-control study was performed including 62 patients with gastric cancer and 61 healthy controls. Peripheral blood was collected for genetic analysis of MPO-463. RESULTS: There were no significant differences in gender, age, and smoking between the two groups(P>0.05). However, the two groups differed in drinking, family history of gastric cancer, and Helicobacter pylori(HP) infection(P<0.05). The frequencies of MPO-463GG, GA and AA were 87.1%, 11.3% and 1.6%in the study group, and were 72.1%, 23.0%, and 4.9% in the control group, respectively. Carriers of MPO-463 GA or AA had a significantly higher risk of gastric cancer than those of MPO-463 GG(χ(2)=4.253, P<0.05, OR=0.383, 95% CI: 0.151-0.972). Carriers of G allele had a significantly lower risk of gastric cancer compared to carriers of A allele(χ(2)=4.935, P<0.05, OR=0.399, 95% CI: 0.174-0.916). CONCLUSION: MPO-463 G/A polymorphism is associated with gastric cancer with A being a protective gene.

PDGF-BB and TGF-{beta}1 on cross-talk between endothelial and smooth muscle cells in vascular remodeling induced by low shear stress.

Shear stress, especially low shear stress (LowSS), plays an important role in vascular remodeling during atherosclerosis. Endothelial cells (ECs), which are directly exposed to shear stress, convert mechanical stimuli into intracellular signals and interact with the underlying vascular smooth muscle cells (VSMCs). The interactions between ECs and VSMCs modulate the LowSS-induced vascular remodeling. With the use of proteomic analysis, the protein profiles of rat aorta cultured under LowSS (5 dyn/cm(2)) and normal shear stress (15 dyn/cm(2)) were compared. By using Ingenuity Pathway Analysis to identify protein-protein association, a network was disclosed that involves two secretary molecules, PDGF-BB and TGF-ß1, and three other linked proteins, lamin A, lysyl oxidase, and ERK 1/2. The roles of this network in cellular communication, migration, and proliferation were further studied in vitro by a cocultured parallel-plate flow chamber system. LowSS up-regulated migration and proliferation of ECs and VSMCs, increased productions of PDGF-BB and TGF-ß1, enhanced expressions of lysyl oxidase and phospho-ERK1/2, and decreased Lamin A in ECs and VSMCs. These changes induced by LowSS were confirmed by using PDGF-BB recombinant protein, siRNA, and neutralizing antibody. TGF-ß1 had similar influences on ECs as PDGF-BB, but not on VSMCs. Our results suggest that ECs convert the LowSS stimuli into up-regulations of PDGF-BB and TGF-ß1, but these two factors play different roles in LowSS-induced vascular remodeling. PDGF-BB is involved in the paracrine control of VSMCs by ECs, whereas TGF-ß1 participates in the feedback control from VSMCs to ECs.

[Effect of histamine H4 receptor and its antagonist on allergic rhinitis in rats].

OBJECTIVE: To clarify the effect of histamine H4 receptor antagonist, JNJ 7777120, and histamine H1 receptor antagonist, Loratadine, on allergic rhinitis (AR) in rats and to study the role of histamine H4 receptor antagonist and histamine H1 receptor antagonist in the pathogenesis of allergic rhinitis and therapeutic value of their antagonist. METHODS: AR animal model were induced by ovalbumin (OVA) in the Wistar rats, which treated with histamine H4 receptor antagonist and (or) histamine H1 receptor antagonist. The allergic symptoms (sneezing and nasal rubbing), serum total IgE and the levels of cytokines in serum or nasal lavage fluid were measured, the diversity between two groups were observed. Statistical analysis was performed using a SPSS 13.0 software. RESULTS: Compared with AR group with no treatment, the inhibition of nasal symptoms (P < 0.01), a significant decrease in the levels of IgE, IL-4 in serum and Eotaxin in nasal lavage fluid (P < 0.01), a significant increase in the levels of IFN-γ in serum (P < 0.01) after treatment was found. Compared with group treated with Loratadine, inhibition of nasal symptoms (q value were 3.72, 4.16, P < 0.01), a significant increase in the levels of IgE and IL-4 in serum (q value were 8.01, 4.96, P < 0.05), a significant decrease in the levels of IFN-γ in serum (q = 3.18, P < 0.05) in group treated with JNJ 7777120 also, but no significant differences in the levels of Eotaxin in nasal lavage fluid (P > 0.05). Administration of JNJ 7777120 and Loratadine jointly, neither additive effect nor synergistic action were found (P > 0.05). CONCLUSIONS: Histamine H4 receptor is closely related with allergic rhinitis and is important in the pathogenesis of allergic rhinitis, the same as histamine H1 receptor. Histamine H4 receptor antagonist, JNJ 7777120, could relieve symptoms and inflammatory conditions in allergic rhinitis, the effect was weak compared with Loratadine. Neither additive effect nor synergistic action were found between them.